Bone repair and reconstruction is an important clinical problem. It is estimated in United States alone, the number of bone repair procedures is more than 800,000 per year. The traditional biological methods include autografting and allografting of cancellous bone (also known as trabecular bone or spongy bone), applying vascularized grafts of the fibula and iliac crest, and using other bone transport techniques.
Today, bone grafting is increasing and the failure rate is high. In patients who receive various bone grafts, a failure rate ranging from 16% to 50% is reported. The failure rate of autografts is at the lower end of this range, but the need for a second (i.e., donor) site of surgery, limited supply, inadequate size and shape, and the morbidity associated with the donor site are all major issues. Furthermore, the new bone volume maintenance can be problematic due to unpredictable bone resorption. In large defects, the body can resorb the grafts before osteogenesis is complete.
The operating time required for harvesting autografts is expensive and often the donor tissue is scarce. There can be significant donor site morbidity associated with infection, pain, and hematoma. Allografting introduces the risk of disease and/or infection; it may cause a lessening or complete loss of the bone inductive factors. Vascularized grafts require a major microsurgical operative procedure requiring a sophisticated infrastructure. Distraction osteogenesis techniques are often laborious and lengthy processes that are reserved for the most motivated patients.
Tissue engineering osseous tissue by using cells in combination with a synthetic extracellular matrix is a new approach compared to the transplantation of harvested tissues. Numerous tissue-engineering concepts have been proposed to address the need for new bone graft substitutes. One potentially successful repair solution seeks to mimic the success of autografts by removing cells from the patient by biopsy and then growing sufficient quantities of mineralized tissue in vitro on implantable, 3D scaffolds for use as functionally equivalent autogenous bone tissue. In this way, reproducing the intrinsic properties of autogenous bone material creates an ideal bony regeneration environment, which includes the following characteristics: (i) a highly porous, 3D architecture allowing osteoblast, osteoprogenitor cell migration and graft revascularization; (ii) the ability to be incorporated into the surrounding host bone and to continue the normal bone remodeling processes; and (iii) the delivery of bone-forming cells and osteogenic growth factors to accelerate healing and differentiation of local osteoprogenitor cells.
Naturally-derived or synthetic materials are fashioned into scaffolds that, when implanted in the body as temporary structures, provide a template that allows the body's own cells to grow and form new tissues while the scaffold is gradually absorbed. Conventional two-dimensional scaffolds are satisfactory for multiplying cells, but are less satisfactory when it comes to generating functional tissues. For that reason, a three-dimensional (3D) bioresorbable scaffold system is preferred for the generation and maintenance of highly differentiated tissues. Ideally, the scaffold should have the following characteristics: (i) be highly porous with an interconnected pore network for cell growth and flow transport of nutrients and metabolic waste; (ii) be biocompatible and bioresorbable, with controllable degradation and resorption rates so as to substantially match tissue replacement; (iii) have suitable surface chemistry for cell attachment, proliferation and differentiation; (iv) have enough channels to promote vascular integration and (v) have mechanical properties to match those of the tissues at the site of implantation. In vivo, the scaffold structure should protect the inside of the pore network proliferating cells and their extracellular matrix from being mechanically overloaded for a sufficient period of time. This is particularly important for load-bearing tissues such as bone and cartilage. A biomechanically stable scaffold with mechano-induction properties is therefore sought after.
Porosity and pore sizes play a critical role in bone formation in vivo situations. Higher porosity and pore size has shown to result in greater bone ingrowth however the mechanical properties are diminished in such instances. Present limitations thus set an upper function limit for pore size and porosity. Repair of bone tissue, rate of remodeling is thus compromised.
The repair and reconstruction of large bone defects such as in the lengthening of the lower limb, has been a clinical challenge as such. This problem has yet to be solved. Presently none of the approaches proposed thus far have shown long term efficacy that resembles the natural bone. The era of tissue engineering involving stems cells and a suitable scaffold could provide the answer. However, a suitable scaffold has yet to be designed. Ceramics scaffolds such as macro porous hydroxyapatite (HA) (R. Quarto et al, 2001) have been tried with some clinical success. But ceramics are brittle material and the scaffolds are prone to premature fracture. In many cases HA ceramics are crystalline in nature and hence do not render it resorbable even after 6 years. Bioresorbable polymeric scaffolds have been used but none has been designed for long bone tissue applications. Those polymers with high glass transition temperature such as PGA and PLA are also brittle and some degrade too fast, hence are unable to evoke the long term mechano-induction required for proper bone remodeling process. The large volume of acid formation, as a by product of degradation, of those with too short a degradation time, also hinders the proper cell formation and growth of the bone. The other issue is that large scaffolds of this nature do not have enough channels to provide the rich vasculature of blood vessels for drainage of waste products as well as delivery of nutrients over the entire volume. Scaffolds with high porosity also do not have enough mechanical stability to be used for structural bone tissue engineering of the long bones.